The long term goal of this research is to elucidate the pathways and mechanisms by which the midbrain periaqueductal gray (PAG) regulates autonomic functions. The proposed studies use multidisciplinary approaches to test specific hypotheses, suggested by out new pilot data and previous studies, of the role of PAG in cardiovascular regulation. Most investigations of PAG have focused on the role of this structure in analgesia, the "defense and escape reactions", and sexual behavior. Our new results suggests that PAG exerts remarkably potent, selective, bidirectional actions on blood pressure. Pressor and depressor responses elicited by electrical or chemical microstimulation of PAG are obtained from two discrete, longitudinally organized columns of neurons along the rostrocaudal axis of PAG. PAG neurons in the vicinity of these pressor- depressor columns heavily and selectively innervate the rostral ventrolateral medulla (RVM), a major sympathoexcitatory region, and nucleus ambiguous (NA), the source of preganglionic parasympathetic neurons that project to the heart. Additional new results demonstrate that PAG receives robust, highly organized inputs from several forebrain areas specifically implicated in cardiovascular regulation. Our findings show that these forebrain areas focally innervate discrete subregions of PAG, forming distinct longitudinal input columns that span the entire rostrocaudal extent of PAG. These longitudinal input columns from forebrain pressor- depressor areas may selectively target corresponding pressor-depressor columns in PAG, including neurons projecting to known cardiovascular regulatory sites in the medulla. Taken together, our new results suggest that PAG pressor=depressor columns selectively target and functionally engage sympathoexcitatory and vagal cardioinhibitory neurons in RVM and NA. We further hypothesize that forebrain pressor-depressor sites focally target longitudinal columns of PAG pressor-depressor neurons that project to these medullary vasomotor sites. These forebrain-PAG-medullary circuits may function to provide coordinated cardiovascular adjustments during emotional reactions. We will test these hypotheses by a set of highly coordinate anatomical and neurophysiological experiments. At the present time, there is only fragmentary information about the circuits and physiological mechanisms mediating PAG's actions on the nervous system. The proposed research, by closing this gap, will advance our understanding of CNS regulation of the autonomic nervous system. In addition, this research may provide new insights into disturbances in cardiovascular tone (e.g. hypertension) associated with stress and emotional disturbances.